Fungicidal mixtures based on a trizolopyrimidine derivative

ABSTRACT

Fungicidal mixtures, comprising, as active components: 
 
1) the triazolopyrimidine derivative of the formula I,  
                 
and 
 
2) benomyl of the formula II,  
                 
in a synergistically effective amount, methods for controlling harmful fungi using mixtures of compound I and compound II and compositions comprising these mixtures are described.

The present invention relates to fungicidal mixtures, comprising asactive components1) the triazolopyrimidine derivative of the formula I,

and2) benomyl of the formula II,

in a synergistically effective amount.

Moreover, the invention relates to a method for controlling harmfulfungi using mixtures of the compound I with the compound II and to theuse of the compound I with the compound II for preparing such mixturesand to compositions comprising these mixtures.

The compound I,5-chloro-7-(4-methylpiperidin-1-yl)-6-(2,4,6-trifluorophenyl)-[1,2,4]triazolo[1,5-a]pyrimidine,its preparation and its action against harmful fungi are known from theliterature (WO 98/46607).

Mixtures of triazolopyrimidine derivatives with benomyl are known in ageneral manner from EP-A 988 790. The compound I is embraced by thegeneral disclosure of this document, but not explicitly mentioned.Accordingly, the combination of the compound I with benomyl is novel.

The compound II, N-butyl-2-acetylaminobenzimidazole-1-carboxamide, itspreparation and its action against harmful fungi are likewise known fromthe literature (U.S. Pat. No. 3,631,176; common name: benomyl).

The synergistic mixtures of triazolopyrimidines described in EP-A 988790 are described as being fungicidally active against various diseasesof cereals, fruit and vegetables, in particular mildew on wheat andbarley or gray mold on apples. However, the fungicidal action of thesemixtures against harmful fungi from the class of the Oomycetes isunsatisfactory.

The biological behavior of Oomycetes is clearly different from that ofthe Ascomycetes, Deuteromycetes and Basidiomycetes, since Oomycetes arebiologically closer related to algae than to fungi. Accordingly, what isknown about the fungicidal activity of active compounds against “truefungi” such as Ascomycetes, Deuteromycetes and Basidiomycetes can beapplied only to a very limited extent to Oomycetes.

Oomycetes cause economically relevant damage to various crop plants. Inmany regions, infections by Phytophthora infestans in the cultivation ofpotatoes and tomatoes are the most important plant diseases. Inviticulture, considerable damage is caused by peronospora of grapevines.

There is a constant demand for novel compositions against Oomycetes inagriculture, since there is already widespread resistance of the harmfulfungi to the products established in the market, such as, for example,metalaxyl and active compounds of a similar structure.

It is an object of the present invention, with a view to effectiveresistance management and an effective control of harmful fungi from theclass of the Oomycetes at application rates which are as low aspossible, to provide mixtures which, at a minimum possible total amountof active compounds applied, are sufficiently active against the harmfulfungi.

We have found that this object is achieved by the mixtures defined atthe outset. Moreover, we have found that simultaneous, that is joint orseparate, application of the compound I and the compound II orsuccessive application of the compound I and the compound II allowsbetter control of Oomycetes than is possible with the individualcompounds (synergistic mixtures).

When preparing the mixtures, it is preferred to employ the pure activecompounds I and II, to which further active compounds against harmfulfungi or against other pests, such as insects, arachnids or nematodes,or else herbicidal or growth-regulating active compounds or fertilizerscan be added according to need.

Further suitable active compounds in the above sense are in particularactive compounds selected from the following groups:

-   -   acylalanines, such as benalaxyl, metalaxyl, ofurace or oxadixyl,    -   amine derivatives, such as aldimorph, dodine, dodemorph,        fenpropimorph, fenpropidin, guazatine, iminoctadine, spiroxamine        or tridemorph,    -   anilinopyrimidines, such as pyrimethanil, mepanipyrim or        cyprodinyl,    -   antibiotics, such as cycloheximide, griseofulvin, kasugamycin,        natamycin, polyoxin or streptomycin,    -   azoles, such as bitertanol, bromoconazole, cyproconazole,        difenoconazole, dinitroconazole, epoxiconazole, fenbuconazole,        fluquinconazole, flusilazole, hexaconazole, imazalil,        ipconazole, metconazole, myclobutanil, penconazole,        propiconazole, prochloraz, prothioconazole, simeconazole,        tebuconazole, tetraconazole, triadimefon, triadimenol,        triflumizole or triticonazole,    -   dicarboximides, such as iprodione, myclozolin, procymidone or        vinclozolin,    -   dithiocarbamates, such as ferbam, nabam, maneb, mancozeb, metam,        metiram, propineb, polycarbamate, thiram, ziram or zineb,    -   heterocyclic compounds, such as anilazine, boscalid,        carbendazim, carboxin, oxycarboxin, cyazofamid, dazomet,        dithianon, famoxadone, fenamidone, fenarimol, fuberidazole,        flutolanil, furametpyr, isoprothiolane, mepronil, nuarimol,        picobenzamide, probenazole, proquinazid, pyrifenox, pyroquilon,        quinoxyfen, silthiofam, thiabendazole, thifluzamide,        thiophanate-methyl, tiadinil, tricyclazole or triforine,    -   copper fungicides, such as Bordeaux mixture, copper oxychloride,        copper hydroxide, copper oxide, (basic) copper sulfate or copper        oxychloride sulfate,    -   nitrophenyl derivatives, such as binapacryl, dinocap, dinobuton        or nitrophthalisopropyl,    -   phenylpyrroles, such as fenpiclonil or fludioxonil,    -   sulfur,    -   other fungicides, such as acibenzolar-S-methyl, benthiavalicarb,        carpropamid, chlorothalonil, cyflufenamid, cymoxanil, dazomet,        diclomezine, diclocymet, diethofencarb, edifenphos, ethaboxam,        fenhexamid, fentin acetate, fenoxanil, ferimzone, fluazinam,        fosetyl, fosetyl-aluminum, iprovalicarb, hexachlorobenzene,        metrafenone, pencycuron, propamocarb, phthalide,        tolclofos-methyl, quintozene or zoxamide,    -   strobilurins, such as azoxystrobin, dimoxystrobin,        fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin,        picoxystrobin, pyraclostrobin or trifloxystrobin,    -   sulfenic acid derivatives, such as captafol, captan,        dichlofluanid, folpet or tolylfluanid,    -   cinnamides and analogous compounds, such as dimethomorph,        flumetover or flumorph.

In one embodiment of the mixtures according to the invention, thecompounds I and II are admixed with a further fungicide III or twofungicides III and IV.

Mixtures of the compounds I and II with a component III are preferred.Particularly preferred are mixtures of the compounds I and II.

The mixtures of the compound I and the compound II or the simultaneous,that is joint or separate, use of the compound I and the compound II aredistinguished by being very highly active against phytopathogenic fungifrom the class of the Oomycetes, in particular of Phytophthora infestanson potatoes and tomatoes and Plasmopara viticola on grapevines. Some ofthem act systemically and can be used as foliar- and soil-actingfungicides to protect plants.

They are particularly important for controlling Oomycetes on variouscrop plants such as vegetable plants (for example cucumbers, beans andcucurbits), potatoes, tomatoes, grapevines and the corresponding seeds.

They are particularly suitable for controlling late blight on tomatoesand potatoes caused by Phytophthora infestans and downy mildew ofgrapevines (peronospora of grapevines) caused by Plasmopara viticola.

In addition, the combination according to the invention of the compoundsI and II is also suitable for controlling other pathogens, such as, forexample, Septoria and Puccinia species in cereals and Alternaria andBoytritis species in vegetables, fruit and grapevines.

The compound I and the compound II can be applied simultaneously, thatis jointly or separately, or in succession, the sequence, in the case ofseparate application, generally not having any effect on the result ofthe control measures.

The compound I and the compound II are usually applied in a weight ratioof from 100:1 to 1:100, preferably from 10:1 to 1:50, in particular from5:1 to 1:20.

If appropriate, the components III and IV are amixed with the compound Iin a ratio of from 20:1 to 1:20.

Depending on the type of compound and the desired effect, theapplication rates of the mixtures according to the invention are from 5g/ha to 2 000 g/ha, preferably from 50 to 1500 g/ha, in particular from50 to 750 g/ha.

Correspondingly, the application rates for the compound I are generallyfrom 1 to 1000 g/ha, preferably from 10 to 750 g/ha, in particular from20 to 500 g/ha.

Correspondingly, the application rates for the compound II are generallyfrom 1 to 1000 g/ha, preferably from 10 to 750 g/ha, in particular from20 to 500 g/ha.

In the treatment of seed, application rates of mixture are generallyfrom 1 to 1000 g/100 kg of seed, preferably from 1 to 200 g/100 kg, inparticular from 5 to 100 g/100 kg.

In the control of phytopathogenic harmful fungi, the separate or jointapplication of the compound I and the compound II or of the mixtures ofthe compound I and the compound II is carried out by spraying or dustingthe seeds, the plants or the soils before or after sowing of the plantsor before or after emergence of the plants.

The mixtures according to the invention, or the compounds I and II, canbe converted into the customary formulations, for example solutions,emulsions, suspensions, dusts, powders, pastes and granules. The useform depends on the particular intended purpose; in each case, it shouldensure a fine and even distribution of the compound according to theinvention.

The formulations are prepared in a known manner, for example byextending the active compound with solvents and/or carriers, if desiredusing emulsifiers and dispersants. Solvents/auxiliaries suitable forthis purpose are essentially:

-   -   water, aromatic solvents (for example Solvesso products,        xylene), paraffins (for example mineral oil fractions), alcohols        (for example methanol, butanol, pentanol, benzyl alcohol),        ketones (for example cyclohexanone, gamma-butyrolactone),        pyrrolidones (NMP, NOP), acetates (glycol diacetate), glycols,        fatty acid dimethylamides, fatty acids and fatty acid esters. In        principle, solvent mixtures may also be used,    -   carriers such as ground natural minerals (for example kaolins,        clays, talc, chalk) and ground synthetic minerals (for example        highly disperse silica, silicates); emulsifiers such as nonionic        and anionic emulsifiers (for example polyoxyethylene fatty        alcohol ethers, alkylsulfonates and arylsulfonates) and        dispersants such as lignin-sulfite waste liquors and        methylcellulose.

Suitable surfactants used are alkali metal, alkaline earth metal andammonium salts of lignosulfonic acid, naphthalenesulfonic acid,phenolsulfonic acid, dibutylnaphthalenesulfonic acid,alkylarylsulfonates, alkyl sulfates, alkylsulfonates, fatty alcoholsulfates, fatty acids and sulfated fatty alcohol glycol ethers,furthermore condensates of sulfonated naphthalene and naphthalenederivatives with formaldehyde, condensates of naphthalene or ofnaphthalenesulfonic acid with phenol and formaldehyde, polyoxyethyleneoctylphenol ether, ethoxylated isooctylphenol, octylphenol, nonylphenol,alkylphenol polyglycol ethers, tributylphenyl polyglycol ether,tristearylphenyl polyglycol ether, alkylaryl polyether alcohols,alcohol- and fatty alcohol ethylene oxide condensates, ethoxylatedcastor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxypropylene,lauryl alcohol polyglycol ether acetal, sorbitol esters, lignosulfitewaste liquors and methylcellulose.

Substances which are suitable for the preparation of directly sprayablesolutions, emulsions, pastes or oil dispersions are mineral oilfractions of medium to high boiling point, such as kerosene or dieseloil, furthermore coal tar oils and oils of vegetable or animal origin,aliphatic, cyclic and aromatic hydrocarbons, for example toluene,xylene, paraffin, tetrahydronaphthalene, alkylated naphthalenes or theirderivatives, methanol, ethanol, propanol, butanol, cyclohexanol,cyclohexanone, isophorone, highly polar solvents, for example dimethylsulfoxide, N-methylpyrrolidone or water.

Powders, materials for spreading and dustable products can be preparedby mixing or concomitantly grinding the active substances with a solidcarrier.

Granules, for example coated granules, impregnated granules andhomogeneous granules, can be prepared by binding the active compounds tosolid carriers. Examples of solid carriers are mineral earths such assilica gels, silicates, talc, kaolin, attaclay, limestone, lime, chalk,bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate,magnesium sulfate, magnesium oxide, ground synthetic materials,fertilizers, such as, for example, ammonium sulfate, ammonium phosphate,ammonium nitrate, ureas, and products of vegetable origin, such ascereal meal, tree bark meal, wood meal and nutshell meal, cellulosepowders and other solid carriers.

In general, the formulations comprise from 0.01 to 95% by weight,preferably from 0.1 to 90% by weight, of the active compounds. In thiscase, the active compounds are employed in a purity of from 90% to 100%,preferably 95% to 100% (according to NMR spectrum).

The following are examples of formulations: 1. Products for dilutionwith water

A) Water-Soluble Concentrates (SL)

10 parts by weight of the active compounds are dissolved in water or ina water-soluble solvent. As an alternative, wetters or other auxiliariesare added. The active compound dissolves upon dilution with water.

B) Dispersible Concentrates (DC)

20 parts by weight of the active compounds are dissolved incyclohexanone with addition of a dispersant, for examplepolyvinylpyrrolidone. Dilution with water gives a dispersion.

C) Emulsifiable Concentrates (EC)

15 parts by weight of the active compounds are dissolved in xylene withaddition of calcium dodecylbenzenesulfonate and castor oil ethoxylate(in each case 5% strength). Dilution with water gives an emulsion.

D) Emulsions (EW, EO)

40 parts by weight of the active compounds are dissolved in xylene withaddition of calcium dodecylbenzenesulfonate and castor oil ethoxylate(in each case 5% strength). This mixture is introduced into water bymeans of an emulsifier machine (Ultraturrax) and made into a homogeneousemulsion. Dilution with water gives an emulsion.

E) Suspensions (SC, OD)

In an agitated ball mill, 20 parts by weight of the active compounds arecomminuted with addition of dispersants, wetters and water or an organicsolvent to give a fine active compound suspension. Dilution with watergives a stable suspension of the active compound.

F) Water-Dispersible Granules and Water-Soluble Granules (WG, SG)

50 parts by weight of the active compounds are ground finely withaddition of dispersants and wetters and made as water-dispersible orwater-soluble granules by means of technical appliances (for exampleextrusion, spray tower, fluidized bed). Dilution with water gives astable dispersion or solution of the active compound.

G) Water-Dispersible Powders and Water-Soluble Powders (WP, SP)

75 parts by weight of the active compounds are ground in a rotor-statormill with addition of dispersants, wetters and silica gel. Dilution withwater gives a stable dispersion or solution of the active compound.

2. Products to be Applied Undiluted

H) Dustable Powders (DP)

5 parts by weight of the active compounds are ground finely and mixedintimately with 95% of finely divided kaolin. This gives a dustableproduct.

I) Granules (GR, FG, GG, MG)

0.5 part by weight of the active compounds is ground finely andassociated with 95.5% carriers. Current methods are extrusion,spray-drying or the fluidized bed. This gives granules to be appliedundiluted.

J) ULV Solutions (UL)

10 parts by weight of the active compounds are dissolved in an organicsolvent, for example xylene. This gives a product to be appliedundiluted.

The active compounds can be used as such, in the form of theirformulations or the use forms prepared therefrom, for example in theform of directly sprayable solutions, powders, suspensions ordispersions, emulsions, oil dispersions, pastes, dustable products,materials for spreading, or granules, by means of spraying, atomizing,dusting, spreading or pouring. The use forms depend entirely on theintended purposes; they are intended to ensure in each case the finestpossible distribution of the active compounds according to theinvention.

Aqueous use forms can be prepared from emulsion concentrates, pastes orwettable powders (sprayable powders, oil dispersions) by adding water.To prepare emulsions, pastes or oil dispersions, the substances, as suchor dissolved in an oil or solvent, can be homogenized in water by meansof a wetter, tackifier, dispersant or emulsifier. However, it is alsopossible to prepare concentrates composed of active substance, wetter,tackifier, dispersant or emulsifier and, if appropriate, solvent or oil,and such concentrates are suitable for dilution with water.

The active compound concentrations in the ready-to-use preparations canbe varied within relatively wide ranges. In general, they are from0.0001 to 10%, preferably from 0.01 to 1%.

The active compounds may also be used successfully in theultra-low-volume process (ULV), it being possible to apply formulationscomprising over 95% by weight of active compound, or even to apply theactive compound without additives.

Oils of various types, wetters, adjuvants, herbicides, fungicides, otherpesticides, or bactericides may be added to the active compounds, even,if appropriate, not until immediately prior to use (tank mix). Theseagents can be admixed with the agents according to the invention in aweight ratio of 1:10 to 10:1.

The compounds I and II, the mixtures or the corresponding formulationsare applied by treating the harmful fungi, the plants, seeds, soils,areas, materials or spaces to be kept free from them with a fungicidallyeffective amount of the mixture or, in the case of separate application,of the compounds I and II. Application can be carried out before orafter infection by the harmful fungi.

The fungicidal action of the compound and the mixtures can bedemonstrated by the following experiments:

The active compounds, separately or jointly, were prepared as a stocksolution comprising 0.25% by weight of active compound in acetone orDMSO. 1% by weight of the emulsifier Uniperol® EL (wetting agent havingemulsifying and dispersant action based on ethoxylated alkylphenols) wasadded to this solution, and the mixture was diluted with water to thedesired concentration.

USE EXAMPLE Activity Against peronospora of Grapevines Caused byPlasmopara viticola

Leaves of potted vines of the cultivar “Müller-Thurgau” were sprayed torunoff point with an aqueous suspension having the concentration ofactive compound stated below. The next day, the undersides of the leaveswere inoculated with an aqueous zoospore suspension of Plasmoparaviticola. The grapevines were then initially placed in awater-vapor-saturated chamber at 24° C. for 48 hours and then in agreenhouse at 20-30° C. for 5 days. After this period of time, theplants were again placed in a humid chamber for 16 hours to promotesporangiophore eruption. The extent of the development of the disease onthe undersides of the leaves was then determined visually.

The visually determined percentages of infected leaf areas wereconverted into efficacies in % of the untreated control:

The efficacy (E) is calculated as follows using Abbot's formula:E=(1−α/β)−100α corresponds to the fungicidal infection of the treated plants in % andβ corresponds to the fungicidal infection of the untreated (control)plants in %

An efficacy of 0 means that the infection level of the treated plantscorresponds to that of the untreated control plants; an efficacy of 100means that the treated plants are not infected.

The expected efficacies of mixtures of active compounds were determinedusing Colby's formula (Colby, S. R. “Calculating synergistic andantagonistic responses of herbicide combinations”, Weeds, 15, 20-22,1967) and compared with the observed efficacies.

Colby's formula:E=x+y−x·y/100

-   E expected efficacy, expressed in % of the untreated control, when    using the mixture of the active compounds A and B at the    concentrations a and b-   x efficacy, expressed in % of the untreated control, when using the    active compound A at the concentration a-   y efficacy, expressed in % of the untreated control, when using the    active compound B at the concentration b

The comparative compounds used were the compounds A and B known from thebenomyl mixtures described in EP-A 988 790:

TABLE A Individual active compounds Concentration of active Efficacy Ex-compound in the spray in % of the ample Active compound liquor [ppm]untreated control 1 — Control (untreated) (84% infection) 2 I 1 17 0.250 3 II (benomyl) 4 0 1 0 4 Comparison A 1 0 0.25 0 5 Comparison B 1 170.25 5

TABLE B Mixtures according to the invention Mixture of active compoundsEx- Concentration ample Mixing ratio Observed efficacy Calculatedefficacy*) 6 I + II 29 0 0.25 + 4 ppm 1:16 7 I + II 41 17 1 + 1 ppm 1:1*) efficacy calculated using Colby's formula

TABLE C Comparative experiments - mixtures known from EP-A 988 790Mixture of active compounds Ex- Concentration ample Mixing ratioObserved efficacy Calculated efficacy*) 8 A + II 0 0 0.25 + 4 ppm 1:16 9A + II 0 0 1 +1 ppm 1:1 10 B + II 0 5 0.25 + 4 ppm 1:16 11 B + II 5 171 + 1 ppm 1:1*) efficacy calculated using Colby's formula

The test results show that in all mixing ratios the observed efficacy ofthe mixtures according to the invention is considerably higher than thatpredicted using Colby's formula, whereas the benomyl mixtures, knownfrom EP-A 988 790, of the comparative active compounds are not effectivein controlling Oomycetes.

1. A fungicidal mixture, comprising as active components 1) thetriazolopyrimidine derivative of the formula I

and 2) benomyl of the formula II,

in a synergistically effective amount.
 2. A fungicidal mixture,comprising the compound of the formula I and the compound of the formulaII in a weight ratio of from 100:1 to 1:100.
 3. A fungicidalcomposition, comprising a liquid or solid carrier and a mixture asclaimed in claim 1 or
 2. 4. A method for controlling harmful fungi fromthe class of the Oomycetes, which comprises treating the fungi, theirhabitat or the seed, the soil or the plants to be protected againstfungal attack with an effective amount of the compound I and thecompound II as set forth in claim
 1. 5. A method as claimed in claim 4,wherein the compounds I and II as set forth in claim 1 are appliedsimultaneously, that is jointly or separately, or in succession.
 6. Amethod as claimed in claim 4, wherein the mixture as claimed in claim 1is applied to the soil or the plants to be protected against fungalattack in an amount of from 5 g/ha to 2000 g/ha.
 7. A method as claimedin claim 4, wherein the mixture as claimed in claim 1 is applied in anamount of from 1 to 1000 g/100 kg of seed.
 8. A method as claimed inclaim 4, wherein the harmful fungus Plasmopara viticola is controlled.9. Seed, comprising the mixture as claimed in claim 1 or 2 in an amountof from 1 to 1000 g/100 kg.
 10. The use of the compound I and thecompound II as set forth in claim 1 for preparing a composition suitablefor controlling Oomycetes.
 11. A method as claimed in claim 4, whereinthe mixture as claimed in claim 2 is applied to the soil or the plantsto be protected against fungal attack in an amount of from 5 g/ha to2000 g/ha.
 12. A method as claimed in claim 5, wherein the mixture asclaimed in claim 1 is applied in an amount of from 1 to 1000 g/100 kg ofseed.
 13. A method as claimed in claim 4, wherein the mixture as claimedin claim 2 is applied in an amount of from 1 to 1000 g/100 kg of seed.14. A method as claimed in claim 5, wherein the mixture as claimed inclaim 2 is applied in an amount of from 1 to 1000 g/100 kg of seed.